Is Diagnosis of Low-Grade Urothelial Carcinoma Possible in Urine Cytology?

Background: Urine cytology is a useful modality, primarily for the diagnosis and follow-up surveillance of high-grade urothelial carcinoma (HGUC). Its utility in diagnosing low-grade urothelial carcinoma (LGUC) remains controversial because of low reported sensitivity compared to cystoscopy.

Aim: To study the cytomorphology of LGUC in voided urine samples and analyze its utility in diagnosis.

Materials And Methods: This is a retrospective study of one year, including 48 voided urine samples in cases which were confirmed as LGUC on subsequent histology. Urine cytology smears of these cases, originally stained with Papanicolaou stain were reviewed, critically analyzed and the specific cytomorphologic and cystoscopic findings were documented.

Results: On review 18 samples were re-categorized as LGUC which included 10 samples initially diagnosed as Negative for HGUC, 2 as Atypical Urothelial Cells - Not Otherwise Specified (AUC-NOS) and 6 as Suspicious for Carcinoma. In addition, another 3 samples with initial diagnosis of LGUC remained as LGUC on review. Thus, a total of 21 LGUC samples were identified after the review. 26 (54%) samples with a diagnosis of negative for HGUC remained negative even after review, as the tumor cells were not identified either due to sampling error or unrecognizable morphology. One (2%) samples of AUC-NOS remained the same on review due to very scant atypical cells. In 21 LGUC samples, cytology showed a dual population of benign differentiated urothelial cells and small urothelial cells with subtle nuclear atypia such as irregular and thickened nuclear membrane with increased nuclear cytoplasmic ratio. In 12 false negative LGUC samples, the diagnostic cells were camouflaged by their subtle nuclear atypia coupled with an overwhelming background of differentiated benign urothelial cells as both appeared almost similar in morphology. Papillary fragments were identified only in 2 samples.

Conclusions: Diagnosis of LGUC on cytology is challenging and depends on the presence of diagnostic cells, pick up of diagnostic cells on screening and accurate interpretation. Special attention to papillary fragments and aforementioned nuclear atypia should be paid as tumor cells may resemble normal urothelial cells and can be easily missed.